Design, synthesis and cytotoxic screening of dimedone derivatives as antitumor agents / (Record no. 177051)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 10946namaa22004571i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | EG-GICUC |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20251227101723.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 251226s2025 ua a|||frm||| 000 0 eng d |
| 040 ## - CATALOGING SOURCE | |
| Original cataloguing agency | EG-GICUC |
| Language of cataloging | eng |
| Transcribing agency | EG-GICUC |
| Modifying agency | EG-GICUC |
| Description conventions | rda |
| 041 0# - LANGUAGE CODE | |
| Language code of text/sound track or separate title | eng |
| Language code of summary or abstract | eng |
| -- | ara |
| 049 ## - Acquisition Source | |
| Acquisition Source | Deposit |
| 082 04 - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 615.19 |
| 092 ## - LOCALLY ASSIGNED DEWEY CALL NUMBER (OCLC) | |
| Classification number | 615.19 |
| Edition number | 21 |
| 097 ## - Degree | |
| Degree | Ph.D |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) | |
| Local Call Number | Cai01.08.04.Ph.D.2025.Mo.D |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Mohammed Abdullah Fathi Hara, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Design, synthesis and cytotoxic screening of dimedone derivatives as antitumor agents / |
| Statement of responsibility, etc. | by Mohammed Abdullah Fathi Hara ; Supervision Prof. Dr. Mohammed Kamal Abdelhameed Sayed, Prof. Dr. Khaled Omar Ahmed Mohamed, Prof. Dr. Mohamed Ramadan Eisa, Prof. Dr. Ehab Saadeldin Hassan Alanwar Taher. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | تصميم وتشييد وفحص السمية الخلوية لمشتقات الديميدون كعوامل مضادة للأورام |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2025. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 137 pages : |
| Other physical details | illustrations ; |
| Dimensions | 25 cm. + |
| Accompanying material | CD. |
| 336 ## - CONTENT TYPE | |
| Content type term | text |
| Source | rda content |
| 337 ## - MEDIA TYPE | |
| Media type term | Unmediated |
| Source | rdamedia |
| 338 ## - CARRIER TYPE | |
| Carrier type term | volume |
| Source | rdacarrier |
| 502 ## - DISSERTATION NOTE | |
| Dissertation note | Thesis (Ph.D)-Cairo University, 2025. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 118-137. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | The current study involves the design and synthesis of seven novel series of dimedone-based <br/>compounds. The anticancer activity of all synthesized compounds was screened for anticancer <br/>activity against six human cancer cell lines. <br/>The experimental section was carried out in 7 schemes: <br/>Scheme 1: Includes the preparation of starting compound 3-((4-bromophenyl)amino)-5,5-<br/>dimethylcyclohex-2-en-1-one (II) via the condensation of dimedone (I) with p-bromoaniline in <br/>toluene. The corresponding compound III was obtained through the multicomponent double <br/>Mannich reaction of compound II with p-amino-acetophenone and formalin. Furthermore, <br/>chalcone reaction of octahydroquinazoline (III) with appropriate aldehydes to produce target <br/>compounds IVa-k. <br/>Scheme 2: Include the reaction of dimedone (I) with the p-phenylenediamine in toluene <br/>afforded the desired Schiff base enaminone V. Acetylation reaction of enaminone V with <br/>chloroacetyl chloride in the presence of triethylamine afforded a novel chloroacetamide derivative <br/>(VI). Finally, the N,N’-diaryl 2-aminoacetamides VIIIa-c were synthesized through the N-<br/>alkylation reaction of the chloroacetamide intermediate (VI) with the appropriate aromatic amines. <br/>Scheme 3: Include the reaction of appropriate phenacyl bromide and thiourea under reflux in <br/>ethanol to obtain the desired phenyl thiazoles (IXa-c). Finally, N-alkylation reaction of the novel <br/>chloroacetamide intermediate (VI) with the appropriate phenyl thiazoles (IXa-c) to produce target <br/>compounds Xa-c. <br/>Scheme 4: A mixture of equimolar amounts of 5,5-dimethylcyclohexan-1,3-dione (dimedone) <br/>(I) and p-aminophenol in toluene was heated under reflux to produce the reported enaminone XI. <br/>Finally, O-Alkylation reaction of enaminone XI with appropriate alkyl halides (XIIa-c) afforded <br/>the N-aryl acetamides (XIIIa-c). <br/>Scheme 5: To a mixture of 4-(4-substitutedphenyl)thiazol-2-amines IXa-d and triethylamine, <br/>chloroacetyl chloride was added to obtain the corresponding thiazolyl alkyl chlorides XIVa-d. <br/>After that, O-Alkylation reaction of enaminone XI with appropriate thiazolyl alkyl halides XIVa-d <br/>afforded the N-(4-(aryl)thiazol-2-yl)acetamides XVa-d. <br/>Scheme 6: The reaction of appropriate benzoic acid ethyl esters XVia-g and hydrazine <br/>hydrate 100% to obtain the corresponding hydrazides XVIIa-g which were cyclocondensed to <br/>obtain the corresponding oxadiazoles XVIIIa-g. Finally, 2-diarylthio-N-aryl acetamides XIXa-g <br/> were synthesized by S-alkylation of the chloroacetamide intermediate (VI) with appropriate <br/>thiophenyl oxadiazoles XVIIIa-g. <br/>Scheme 7: Involving benzoylation of the appropriate benzoic acid hydrazides XVIIa-g with <br/>phenyl isothiocyanate to obtain the corresponding carbothioamides XXa-g which cyclocondesed <br/>with NaOH in absolute alcohol to give the corresponding diphenyl triazoles XXIa-g. Finally, S-<br/>alkylation of the acetamide chloride (VI) with the appropriate substitutedphenyl-4-phenyl-4H-<br/>1,2,4-triazole-3-thiols XXIa-g were afforded the target 2-triarylthio-N-aryl acetamides XXIIa-g. <br/>In the way to evaluate the new compounds potencies against different cancer types, the <br/>octahydroquinazolines III and IVa-k were designed with dual inhibition of tubulin <br/>polymerization/Eg5 against HepG-2 cell line. All octahydroquinazolines have been in vitro assayed <br/>against HepG-2 cytotoxicity, Eg5 inhibitory and anti-tubulin polymerization activities. Chalcones <br/>IVg, IVh, and IVj displayed the most cytotoxic potency and anti-tubulin aggregation in <br/>comparison with reference standard colchicine and potential anti-mitotic Eg5 inhibitory activity in <br/>comparison with Monastrol as well. Besides, they exhibited cell cycle arrest at the G2/M phase. <br/>Moreover, good-convinced apoptotic activities have been concluded as overexpression of caspase-<br/>3 levels and tumor suppressive gene p53 in parallel with higher induction of Bax and inhibition of <br/>Bcl-2 biomarkers. <br/>On the other hand, investigation of diaryl acetamide derivatives VIIa-c, Xa-c, XIIIa-c, <br/>XVa-d, XIXa-g and XXIIa-g as tyrosine kinase FMS-3 enzyme (FLT-3) inhibitors with potential <br/>cytotoxic activity against leukemic cells (HL-60). The synthesized compounds were initially tested <br/>for FLT-3 enzyme inhibition. Whereas compounds Xa, XIXb, and XXIIb showed significant <br/>inhibitory activity against the FLT-3 enzyme, surpassing that of the reference drug sorafenib. The <br/>cytotoxicity assessment on HL-60 cells revealed that compound XIXb exhibited the highest <br/>cytotoxicity than the standard drug. Finally, molecular docking studies showed that compound <br/>XIXb exhibited a similar binding pattern to sorafenib with FLT-3 enzyme binding site. <br/>The structural identification of all the newly synthesized compounds was supported by <br/>elemental analysis, IR, 1H NMR, 13C NMR, and a mass spectrometry. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | تتناول هذه الرسالة تصميم وتشييد وفحص السمية الخلوية لمشتقات جديدة من الديميدون ذات نشاط متوقع كمضادات للسرطان. تتكون الرسالة من أربعة أجزاء:<br/>الجزء الأول:<br/>يقدم مقدمة موجزة عن مركب الديميدون بما في ذلك خصائصه الكيميائيه، وطرق التحضير المختلفة، وأنشطته البيولوجية. يلي ذلك مقدمة عن عملية البيروبتوزيز (Pyroptosis)، مع تقديم أمثلة على العوامل المحفزة لها وتصنيفها كيميائا طبقا للمجموعات الوظيفية.<br/>الجزء الثاني:<br/>يتناول أهداف البحث، التي تشمل جميع التعديلات المستخدمة لتشييد مجموعة جديدة من مشتقات أوكتاهيدروكينازولين IVa-k المصممة لتثبيط تبلمر التوبويلين/إنزيم Eg5 ضد خلايا سرطان الكبد.<br/>تم الوصول إلى المشتقات IVa-k من خلال دمج جزيئات الشالكون المضادة للسرطان مع مجموعات متنوعة من الأريلات المختلفة ذات تأثيرات إلكترونية ومحبة للدهون. وقد تم تصميم هذا النمط الهجين بناءً على استراتيجية الدمج الجزيئي بين الموناسترول المضاد للانقسام الميتوزي وعامل تثبيط تجمع التوبويلين الكومباراستيتن أ.<br/>كذلك تم تصميم ثلاثة نماذج فارماكوفورية كمثبطات لإنزيم FLT-3 وكعوامل سامة للخلايا السرطانية. وقد أعتمدت هذه النماذج على التغيرات الجزيئية في جزئي الرأس والروابط الوسيطة مع الاحتفاظ بباقي المركب ثابتا:<br/>النموذج الأول: يتكون من قوالب رئيسية مع حلقات فينيل مستبدلة كرأس.<br/>النموذج الثاني: يشمل قوالب مختلفة مع توسعة للرأس واستبدال النيتروجين بالكبريت في الرابط الوسيط.<br/>النموذج الثالث: تم توسيع الرأس إلى مجموعة ثلاثية الحلقات.<br/>الجزء الثالث:<br/>يناقش الإجراءات التجريبية لتحضير السلاسل IVa-k ، VIIa-c، Xa-c، XIIIa-c، XVa-d، XIXa-g، XXIIa-g. بعد ذلك تم تقييم نشاط مركبات IVa-k في المختبر ضد خلايا HepG-2 لتحديد السمية الخلوية بتركيزات مايكروملارية. أظهرت المركبات IVg، IVh،IVj أعلى نشاط مضاد لتجمع التوبولين، مع نشاط مضاد للانقسام مماثل لمعايير مثل الكولشيسين والموناسترول. وكذلك أظهرت تحليلات تدفق الحمض النووي, أن نفس هذه المركبات الواعدة تسبب توقف دورة الخلية في مرحلة G2/M في الأنقسام الميتوزي. كما أظهرت تلك المركبات زيادة في مؤشرات موت الخلايا المبرمج مثل p53، Bax وCaspase-3 . وقد أشتمل هذا الجزء أيضا على الإرساء الجزيئي لأكثر المركبات فعالية.<br/>الجزء الرابع:<br/>يتناول بالتفصيل إجراءات التشييد، والخصائص الفيزيائية، والبيانات الطيفية للمركبات المستهدفة. كما يشرح منهجية الفحوص البيولوجية في المختبر وخطوات الإرساء الجزيئي لأكثر المركبات فاعلية .<br/>ومن الجدير بالذكر أن الرسالة قد أحتوت على 217 مرجعا بحثيا. |
| 530 ## - ADDITIONAL PHYSICAL FORM AVAILABLE NOTE | |
| Issues CD | Issues also as CD. |
| 546 ## - LANGUAGE NOTE | |
| Text Language | Text in English and abstract in Arabic & English. |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | Pharmaceutical chemistry |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | الكيمياء الصيدلية |
| 653 #1 - INDEX TERM--UNCONTROLLED | |
| Uncontrolled term | Dimedone |
| -- | Eg5 inhibitors |
| -- | CBSIs |
| -- | Michael acceptor |
| -- | Apoptosis |
| -- | Radio chemotherapeutics |
| -- | FLT-3 kinase inhibitors |
| -- | ديميدون |
| -- | مثبطات |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Mohammed Kamal Abdelhameed Sayed |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Khaled Omar Ahmed Mohamed |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Mohamed Ramadan Eisa |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ehab Saadeldin Hassan Alanwar Taher |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2025 |
| Supervisory body | Mohammed Kamal Abdelhameed Sayed |
| -- | Khaled Omar Ahmed Mohamed |
| -- | Mohamed Ramadan Eisa |
| -- | Ehab Saadeldin Hassan Alanwar Taher |
| Universities | Cairo University |
| Faculties | Faculty of Pharmacy |
| Department | Department of Pharmaceutical Organic Chemistry |
| 905 ## - Cataloger and Reviser Names | |
| Cataloger Name | Shimaa |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | Dewey Decimal Classification |
| Koha item type | Thesis |
| Edition | 21 |
| Suppress in OPAC | No |
| Source of classification or shelving scheme | Home library | Current library | Date acquired | Inventory number | Full call number | Barcode | Date last seen | Effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|
| Dewey Decimal Classification | المكتبة المركزبة الجديدة - جامعة القاهرة | قاعة الرسائل الجامعية - الدور الاول | 26.12.2025 | 92937 | Cai01.08.04.Ph.D.2025.Mo.D | 01010110092937000 | 26.12.2025 | 26.12.2025 | Thesis |